MP4-03 ESTROGEN DEFICIENCY ATTENUATES THE THERAPEUTIC EFFECT OF INSULIN-LIKE GROWTH FACTOR-1 ON STRESS URINARY INCONTINENCE IN RATS WITH SIMULATED CHILDBIRTH INJURY

Abstract

INTRODUCTION AND OBJECTIVES: Insulin-like growth factor-1 (IGF-1) plays an important role in cell proliferation, survival and regeneration in various tissues. We recently reported that IGF-1 treatment accelerates recovery from stress urinary incontinence (SUI) induced by stimulated child birth trauma in rats. Because IGF1 reportedly interacts with estrogen, in the present study, we examined whether ovariectomy (OVX) affected the therapeutic effect of IGF-1 on the recovery of SUI induced by simulated childbirth injury in rats. METHODS: Female Sprague-Dawley rats (8 weeks) underwent bilateral OVX or sham operation. After 2 weeks, simulated birth trauma was induced by vaginal distension (VD). Human recombinant IGF-1 (hrIGF-1) (150mg/kg/day) was continuously delivered from 1 day before VD for 7 days using subcutaneous osmotic pumps. At 7 and 14 days after VD, urethral responses were measured using a microtransducer-tipped catheter inserted to the middle urethra from the urethral orifice. The amplitude of urethral responses during sneezing (A-URS), urethral baseline pressure (UBP) and leak point pressure at the time of sneeze (S-LPP) were evaluated. Sneeze was induced by a rat whisker inserted into the nostril. RESULTS: At 7 days after VD, A-URS and UBP, which were reduced by VD, were significantly increased in the sham+IGF-1 group compared to the OVX+vehicle group (A-URS: 14.7 vs. 7.4 cmH2O, UBP: 20.2 vs. 12.7 cmH2O); however there were no significant difference in A-URS or UBP between OVX+IGF-1 and OVX+vehicle groups (Figure). Moreover, S-LPP in the sham+IGF-1 group was significantly elevated compared to the OVX+vehicle group (63.9 vs. 50.9cmH2O) although sneeze-induced SUI was still observed in all groups. At 14 days after VD, sneeze-induced SUI was observed in OVX+vehicle (40%) and OVX+IGF-1 groups (50%) whereas SUI was not observed in sham+vehicle and sham+IGF-1 groups (0%) (Figure). CONCLUSIONS: The therapeutic effects of IGF-1 on SUI induced by simulated childbirth injury were reduced when estrogen deficiency was induced by OVX in rats, suggesting that the efficacy of IGF-1 treatment for childbirth-related SUI could be strengthened in the presence of estrogen.